The proposed research attempts to analyze the basic immunological questions of T cell specificity and nature of T cell receptors using murine virus-infections as models. Effector T cells generated in lymphocytic choriomeningitis or vaccinia virus infection, assayed in vitro by 51Cr release tests or in vivo, are restricted by the H-2K and D regions of H-2. The four main questions under study are: 1. What is the immunological specificity of virus specific T cells in vitro and in vivo? Is it for "altered self" cell surface structures coded in the K and D regions of H-2 or is it for a viral surface antigen in addition to physiological cell-cell interaction mechanisms? The respective association of T cell responses to live or inactivated virus with the various subregions of H-2 will be assessed. 2. Definition and comparison of specificity and cross reactivity of immune T cells in vitro or in vivo generated during infection of mice with various arenaviruses or vaccinia virus. Evaluation of the cross reactivity within one and between different H-2 haplotypes and H-2 mutants in cytotoxicity assays in vitro and in vivo using adoptive transfer models for antiviral protection or transfer of delayed type hypersensitivity. 3. The role of the thymus and of the lymphoreticular system T cell maturation and in triggering cytotoxic T cell responses will be examined in vitro using mixed lymphocyte culture techniques and in vivo using irradiation chimeras and conventional mice. 4. Attempts are made to characterize the idiotype of the T cell receptor for specificity altered self structures by raising antibodies against altered K and D. Antiidiotypic antibodies to these will be assayed for activity against virus-specific effector T cells in vitro. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.